Experts estimate that chronic pain affects nearly 100 million Americans. Most forms of pain result from identifiable causes, which can warn of a real physical problem that needs attention or rest.

Such neuropathic pain is particularly vexing and difficult to treat because there’s no agreed location or physiological mechanism to target for therapy.

However, new research from the University of Alberta, Canada appearing in the Journal of Neurophysiology reports that the place to look is between the nerves that are producing the pain and the spine, rather than from the spine to the brain, according to the senior author, Peter A. Smith.

The American Physiological Society recently published the study, titled “Sciatic Chronic Constriction Injury Produces Cell-Type Specific Changes in the Electrophysiological Properties of Rat Substantia Gelatinosa Neurons.” Sridhar Balasubramanyan, Patrick L. Stemkowski, Martin J. Stebbing and Peter A. Smith conducted the research.

According to Marshall Devor, PhD, a professor at the Institute of Life Sciences, and at the Center for Research on Pain, Hebrew University, Jerusalem, “The results reported in this paper are quite optimistic in terms of the prospects for finding future methods of treatment. First, because if the problem is in the spine or the brain, it’s hard to treat. But if the impact is in the nerve, we have a better idea where to look and it’s also easier to target therapy there.”

Devor adds that the Alberta team “didn’t prove that the central nervous system isn’t involved, but they have shown that the peripheral nerve probably is highly involved.”

Further, “The subject gets complicated quickly and is full of paradoxes,” Smith says. “For instance, in chronic pain there’s often an emotional element. If a patient has post-traumatic stress syndrome, that could make the pain worse because there are overlapping disorders.”

The war in Iraq has highlighted the issue of chronic neuropathic pain in amputations (called “phantom limb pain”) because the rate of amputations is so high compared to previous wars.

Smith says that another “big issue in chronic pain is that two people can have more or less identical injuries, and one gets chronic pain, but the other doesn’t. It may have to do with the immune system and inflammation,” he says.

Another paradox, Smith says, is that “most types of pain are associated with tissue damage and inflammation. Because neuropathic pain can go on for years after initial inflammation has subsided, it is defined as ‘noninflammatory pain.’ Although this definition is accurate, it may have clouded our thinking as to how neuropathic pain is initiated. Current research suggests that an initial transient inflammatory event may set the whole long term pain sequence into motion,” he says.

In the current study, researchers constricted the sciatic nerve of young rats, then studied what changes had occurred in the substantia gelatinosa. This translucent area of the spinal cord is involved in the processing of unpleasant sensations that can be perceived as painful.

According to Devor, much has been made of the theory that neuropathic pain actually imprints changes in the spinal column that are responsible for the long-lived chronic pain.

What the team found, however, was quite surprising.  According to Balasubramanyan, “Given the increase in the excitability of dorsal horn neurons that follows peripheral nerve injury in vivo, and the presence of mechanical hypersensitivity (heightened pain responses) in our experimental animals, the observed changes in the properties of substantia gelatinosa neurons at first seem relatively modest.” For example, CCI [chronic constriction injury] did not promote the generation of spontaneous action potentials in substantia gelatinosa neurons.

They conclude that CCI produced a certain level of bona fide “centralization” in that it “alters the intrinsic properties of the dorsal horn by exerting both pre- and postsynaptic effects on excitatory synaptic transmission and by attenuating inhibitory transmission.” However, the “relative contribution of intrinsic, peripheral and descending mechanisms to nerve injury-induced ‘central hypersensitivity’ is yet to be determined.”

In addition to further studies designed to identify more precisely what changes occur in neuropathic and chronic pain scenarios, Smith says more research needs to be conducted to determine how to treat such pain, regardless of the mechanisms.

For instance, it may be most appropriate to target the initial injury that precipitates the enduring neuropathic pain. In fact, utilizing pre-emptive anesthesia during surgery already does this. The surgeon uses a local anesthetic to deaden the nerves as well as a general anesthetic to immobilize the patent for surgery. Such procedures should be encouraged, Smith says.

Another possibility may be to suppress the immune system for the initial five days after injury. This may curtail the inflammation associated with peripheral nerves that appears to trigger many aspects of neuropathic pain.

In conclusion, Balasubramanyan says, “What needs to be done now is to go back to the periphery and concentrate on finding what physiological mechanisms might be at work closer to the removed part or the original injury site, as in cases of diabetic neuropathy, shingles and surgery.”

   
Source: American Physiological Society